tbuckley/cabot-search huggingface dataset:
Abstract 4221: Aflatoxin exposure in a population-based representative sample of adults in Mexico in 2018
Authors: Adriana Monge, Katherine McGlynn, Luis Santiago-Ruiz, Jose Maria Remes-Troche, Karina Hernandez-Flores, Salvador Villapando-Hernandez, Martin Romero, John Groopman, Martin Lajous
Journal: Cancer Research (2023)

Abstract Importance: Southern Mexico and Guatemala, together represent the region with the highest liver cancer burden in the Americas. There is a higher burden of liver cancer in rural regions in eastern and southern Mexico and remarkably there is an equal number of cases in men and women. Reasons for this increased burden are not clear, but previous studies of food samples have found that contamination of maize with aflatoxin B1 (AFB1), a potent liver carcinogen, is common in the region while HBV and HCV seroprevalence is less than 0.5%. Few examinations of AFB1 levels in persons have been conducted. Objective: To estimate the prevalence of exposure and circulating levels AFB1 in a representative sample of adults living in five regions across Mexico. Study Design: We randomly selected a subsample of 955 adults ≥40 years who participated in Mexico’s National Health and Nutrition Survey 2018 (ENSANUT). These residents were from five states in eastern and southern Mexico and all provided a venous blood sample. We assessed AFB1 levels as pg AFB1-lys/µL in serum using mass spectrometry. The limits of detection and quantification were both 0.010 pg/μL. Results: The mean age of participants was 56 years (± SD 11.7) and 54% were female. The overall prevalence of AFB1-lys detection was 92% (95% confidence intervals; 95%CI 88, 94%). The region with the lowest prevalence, 88% (95%CI 78, 94%), was Chiapas and the region with the highest prevalence was Veracruz 95% (95%CI 84, 98). Median AFB1 was 0.127 pg AFB1-lys/µL (interquartile range; IQR 0.054, 0.446) with a range from 0.066 (IQR, 0.033, 0.147) in Yucatán to 0.476 (IQR, 0.199, 1.355) in Veracruz. AFB1 exposure levels were higher in persons aged ≥60 years, men, and participants living in rural areas. We observed decreasing levels of AFB1 exposure with increasing socioeconomic status. Conclusions: In a representative sample of adults in eastern and southern Mexico we observed a high prevalence of exposure to AFB1. For certain regions, AFB1 levels are comparable to those in Guatemala. These results suggest that AFB1 may be related to the increased burden of liver cancer in eastern and southern Mexico. Citation Format: Adriana Monge, Katherine McGlynn, Luis Santiago-Ruiz, Jose Maria Remes-Troche, Karina Hernandez-Flores, Salvador Villapando-Hernandez, Martin Romero, John Groopman, Martin Lajous. Aflatoxin exposure in a population-based representative sample of adults in Mexico in 2018. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4221.
Abstract 2199: Novel urinary marker for diagnosis and prognosis of neuroblastoma
Authors: Akinari Hinoki, Hizuru Amano, Hiroo Uchida, Atsushi Narita, Shun Kumano, Mayumi Abe, Minoru Sakairi, Chiyoe Shirota, Wataru Sumida, Satoshi Makita, Yoshiyuki Takahashi, Tsuyoshi Osawa
Journal: Cancer Research (2023)

Abstract Background and Aim: Urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA) concentrations are widely used for diagnosis of neuroblastomas, which are catecholamine-secreting tumors. As recent advances in mass spectrometry have facilitated the measurement of metabolites present at extremely low concentrations, urinary metabolites with better diagnostic or prognostic utility for detection of neuroblastomas could be identified. This study utilized quantitative analyses using liquid chromatography-mass spectrometry (LC-MS) to evaluate the diagnostic and prognostic performance of a novel biomarker candidate: 3-methoxytyramine sulfate [3-MTS]. Materials and Methods: The concentrations of the three urinary metabolites (HVA, VMA, and 3-MTS) in urine samples of 41 patients with primary neuroblastoma and urine samples of 155 control participants were measured using LC-MS. The cut-off values for these metabolites were the mean + 2 standard deviation values of the control. Linear discriminant analysis was used to evaluate the association of urinary marker candidates with unfavorable risk factors such as the International Neuroblastoma Pathology Classification and MYCN amplification. Results: The sensitivity and specificity were as follows: 3-MTS 90.2%, 94.2%; HVA 87.8%, 96.1%; VMA 87.8%, 96.1%; VMA or HVA+3-MTS 97.6%, 92.3%; HVA+VMA 87.8%, 94.8%; respectively. 3-MTS could differentiate between the cases with favorable and unfavorable histology (AUC =0.950). 3-MTS+VMA differentiated between the cases with MYCN amplification and nonamplification (AUC=0.952). Conclusions: 3-MTS might be a useful urine marker for both diagnosis and prognosis of neuroblastoma. Citation Format: Akinari Hinoki, Hizuru Amano, Hiroo Uchida, Atsushi Narita, Shun Kumano, Mayumi Abe, Minoru Sakairi, Chiyoe Shirota, Wataru Sumida, Satoshi Makita, Yoshiyuki Takahashi, Tsuyoshi Osawa. Novel urinary marker for diagnosis and prognosis of neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2199.
Abstract 5880: The role of SOAT1 on CD8+T cells-mediated immune response in ovarian cancer
Authors: Jiangnan He, Michelle K.Y. Siu, Runying Long, Ruiqian Zhang, Mingo M.H. Yung, Hextan Y. S. Ngan, Karen K.L. Chan
Journal: Cancer Research (2023)

Abstract Introduction: Sterol-O acyltransferase 1 (SOAT1) functions by converting cholesterol and acyl-CoA into cholesterol ester and coA-SH. High SOAT1 expression with its mediated tumorigenesis has been shown in multiple cancers. Studies showed that SOAT1 inhibition by its inhibitors augmented the outcome of immunotherapies, in terms of the immune checkpoint blockades, cancer vaccines, and CAR-T cells, by boosting the function of T cells. However, in order to have a better understanding of the role played by SOAT1 in the tumor microenvironment of ovarian cancer (OC) and optimize strategies of combination immunotherapy, it’s necessary to detect the role of SOAT1 in OC cells on T cell-mediated immune response. Methods: SOAT1 knockdown was manipulated by siRNAs transfection. SOAT1 was inhibited by avasimibe and OC cells were treated in different doses of avasimibe. qPCR was performed to detect gene expressions in ovarian cancer cells. T cells, isolated and activated from healthy donors, were cocultured with SOAT1-silenced and avasimibe pre-treated OC cells and their tumor-conditioned medium (TCM). Flow cytometry analysis was used to measure cytotoxic secretory molecules of human T cells, like IFN-r, TNF-a, and Granzyme B. Results: The downregulation of intracellular cytotoxic cytokines was shown in the T cells cocultured with SOAT1-silenced and avasimibe-pretreated OC cells or treated by their TCM, thereby impairing the cytotoxic capacity of T cells, compared to the corresponding control group. qPCR results showed that several immunosuppressive cytokines, like IL-6, IL-8, TGF- were upregulated in the SOAT1-silenced or avasimibe-treated OC cells. Conclusion: SOAT1 inhibition in ovarian tumor cells impairs CD8+ T cell cytotoxic function, to some extent, via the upregulation of immunosuppressive-related cytokines. Citation Format: Jiangnan He, Michelle K.Y. Siu, Runying Long, Ruiqian Zhang, Mingo M.H. Yung, Hextan Y. S. Ngan, Karen K.L. Chan. The role of SOAT1 on CD8+T cells-mediated immune response in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5880.
Abstract 4830: Uncoupling protein 2 (UCP2) loss of function mediates PDAC tumor suppression by mitochondrial fusion
Authors: Ariana Carolina Acevedo-Diaz, Emily G. Caggiano, Meifang Yu, Cullen Taniguchi
Journal: Cancer Research (2023)

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a dependence on highly active mitochondria to grow and metastasize. We previously found that mitochondrial fusion suppressed PDAC growth and metastasis, leading to improved survival in a preclinical model. The tumor suppressive mechanisms of mitochondrial fusion remain unclear, and thus we explored the role of redox homeostasis through uncoupling protein 2 (UCP2). Methods/Results: Murine pancreatic cancer cells (KPC) with enhanced mitochondrial fusion (sgDrp1) exhibited higher levels of mitochondrial ROS compared to controls targeting GFP (sgGFP), suggesting altered redox homeostasis. We performed RNAseq on these two cell lines and found that sgDRP1 cells exhibited reduced levels of UCP2. The UCP2 protein is known to have indirect antioxidant effects by reducing mitochondrial reactive oxygen species via uncoupling of ATP production from the electron transport chain. We found that abrogating UCP2 in KPC cells reduced its capacity for OXPHOS. Moreover, rescue of UCP2 in sgDrp1 cells restored their mitochondrial activity. Conclusions: Mitochondrial fusion may suppress tumor growth and induce mitophagy by altering redox homeostasis. UCP2 may be a mediator of the tumor suppressive phenotype induced by mitochondrial fusion, thus linking mitochondrial dynamics and PDAC antioxidant strategies. Future Work: These results will be explored for their translation in vivo and the effects of pharmacological inhibition of UCP2, both in vitro and in vivo, via the specific inhibitor Genipin, will be explored. Citation Format: Ariana Carolina Acevedo-Diaz, Emily G. Caggiano, Meifang Yu, Cullen Taniguchi. Uncoupling protein 2 (UCP2) loss of function mediates PDAC tumor suppression by mitochondrial fusion. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4830.
Abstract 3316: Intra-tumor heterogeneity assessment of liver lesions for colorectal cancer patients on CT-scans
Authors: Ridouane Ghermi, Samy Ammari, Gabriel Garcia, Sana Harguem-zayani, Nathalie Lassau, Kathryn Schutte
Journal: Cancer Research (2023)

Abstract The objective is to find a consensus definition of intra-tumor heterogeneity of liver lesions for colorectal cancer patients on computed tomography (CT) scans and to evaluate the prognostic value of the newly defined criteria. 89 patients with colorectal cancer treated by antiangiogenics having standard pretreatment CT-scans were included. Lesions were manually segmented in a previous study. We reached a consensus definition by bringing three radiologists together to determine which criteria make a tumor heterogeneous. We asked two of the three radiologists to score lesions from one to three based on the consensus definition. A subset of 50 lesions was shared between annotators in order to check their agreement. 898 lesions were scored, which corresponds to a median of 6 lesions per patient. We associate a unique heterogeneity score to each patient defined as the difference between the number of very heterogeneous tumors and the number of heterogeneous tumors. The prognostic value of this heterogeneity score was assessed using a Cox regression. Intra-tumor heterogeneity of a single lesion is defined on a scale of one to three: homogeneous (pixels are of similar intensities), heterogeneous (pixels are of different intensities but organized as a ring), very heterogeneous (pixels are of different intensities and randomly organized). We note that the shape of the tumor is not taken into account in the heterogeneity assessment. The two radiologists agreed on the lesion heterogeneity score in 53% of cases. The patient heterogeneity score is significantly prognostic in both the univariate analysis (Kaplan-Meier estimator with median cut-off; p-value = 0.016) and the multivariate analysis (Cox model with control variables including gender, age, weight, treatment and tumor burden; p-value = 0.024). Three radiologists have reached a consensus to define intra-tumor heterogeneity of liver lesions for colorectal patients. According to this definition, intra-tumor heterogeneity was shown to be a prognostic factor. Citation Format: Ridouane Ghermi, Samy Ammari, Gabriel Garcia, Sana Harguem-zayani, Nathalie Lassau, Kathryn Schutte. Intra-tumor heterogeneity assessment of liver lesions for colorectal cancer patients on CT-scans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3316.
Abstract 3617: Investigating a role for PIKfyve in cell migration and invasion of clear cell renal cell carcinoma
Authors: Jolène Cormier, Sandra Turcotte
Journal: Cancer Research (2023)

Abstract Introduction. Clear cell renal cell carcinoma (ccRCC) is the most frequent type of kidney cancer. These highly vascularized tumors are characterized by mutations that inactivate the von Hippel-Lindau (VHL) tumor suppressor gene. About 30 % of patients present metastasis at diagnosis and 30-40% of patients with localized tumors relapse after surgery. Unfortunately, metastatic ccRCC remains incurable and are resistant to standard therapies. Our studies demonstrated that ccRCC with a loss of VHL can be targeted using a small molecule named STF-62247. This molecule blocks the autophagic flux causing enlargement of endolysosomes leading to cell death. More recently, we identified the lipid kinase PIKfyve as a target of STF-62247. A central complex assuring the functionality of the lysosome is formed by the lipid kinase PIKfyve, the scaffold protein ArPIKfyve (Vac14), and the phosphatase Sac3 (Fig4). Interestingly, PIKfyve has shown to play a role in cell migration but the mechanisms are not well understood. Objectives. Our project aims to i) assess a role for PIKfyve in ccRCC migration/invasion, ii) evaluate the potential of PIKfyve inhibitors on angiogenesis, and iii) assess the effect of PIKfyve inhibitors or genetic knockdown of PIKfyve, Vac14 or Fig4 on tumor growth in vivo. Methods and Results. PIKfyve, Vac14 and Fig4 gene expression were modified using CRISPR/Cas9 (Cr) or the SMARTvectorTM Inducible Lentiviral shRNA system. qRT-PCR and western blot validated our models. Results obtained in Cr.PIKfyve and Cr.Vac14 indicated that loss of Vac14 decreased survival of VHL-deficient ccRCC. Moreover, our recent results show that migration measured by wound healing assay is reduced in CRISPR cells compared to control. To investigate a role for PIKfyve in angiogenesis, tube formation assay was performed in treated cells with PIKfyve inhibitors. Our results indicated a reduction in tube formation in STF-62247 and apilimod treated cells. Furthermore, we will use the proteome profiler human angiogenesis array to identify angiogenic proteins linked to PIKfyve activity. Conclusion. Understanding how PIKfyve is involved in the process of angiogenesis would play a major role in the knowledge for new targeted therapies inkidney cancer. Citation Format: Jolène Cormier, Sandra Turcotte. Investigating a role for PIKfyve in cell migration and invasion of clear cell renal cell carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3617.
Abstract 5326: Comparison of CAR-T cell-mediated cytotoxicity assays with suspension tumor cells using high-throughput plate-based image cytometry method
Authors: Leo Li-Ying Chan, Yu-Jun Sun, Yi-Chun Chen, Wei-Kai Hua, Sariena Chiung-Yuan Wu
Journal: Cancer Research (2023)

Abstract In the recent decade, chimeric antigen receptor (CAR)-T cell therapy has revolutionized strategies for cancer treatments due to its highly effective clinical efficacy and response for B cell malignancies. Currently, there are six CAR-T cell products available in the market including Kymriah, Yescarta, Tecartus, Breyanzi, Abecma, and Carvykt. The success of CAR-T cell therapy has stimulated the increase in the research and development of various CAR constructs to target different tumor types. Therefore, a robust and efficient in vitro potency assay is needed to quickly identify potential CAR gene design from a library of construct candidates. Traditionally, in vitro CAR-T cell-mediated cytotoxicity is assessed using release assays such as 51Cr (radioactivity), calcein (fluorescence), and LDH (enzymatic). However, release assays indirectly measure cell death via molecules released in supernatant and typically limited to only endpoint assays. In addition, handling and disposing of 51Cr hazardous materials is less preferred. Luciferase reporter assay, although highly sensitive, has similar drawbacks as the release assays. Finally, flow cytometry method can directly measure cell death and viability, but can be time-consuming and requires a large number of CAR-T cells when the effector-to-target (E:T) ratio is high. Furthermore, additional steps are required for adherent cells that require trypsinization. Image cytometry methodologies have been utilized for various CAR-T cell-mediated cytotoxicity assay using different fluorescent labeling methods, mainly due to their ease-of-use, ability to capture cell images for verification, and higher throughput performance. In this work, we employed the Celigo high-throughput plate-based Image Cytometer to evaluate and compare two CAR-T cell-mediated cytotoxicity assays using GFP-expressing or fluorescent dye-labeled myeloma and plasmacytoma cells. Performing time- and E:T ratio-dependent CAR-T cell-mediated cytotoxicity assays, the GFP-based method demonstrated higher sensitivity in detecting the level of cytotoxicity when compared to the CMFDA/DAPI viability method. We have established the criteria and considerations for the selection of cytotoxicity assays that are fit-for-purpose to ensure the results produced are meaningful for the specific testing conditions. Citation Format: Leo Li-Ying Chan, Yu-Jun Sun, Yi-Chun Chen, Wei-Kai Hua, Sariena Chiung-Yuan Wu. Comparison of CAR-T cell-mediated cytotoxicity assays with suspension tumor cells using high-throughput plate-based image cytometry method. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5326.
Abstract 5917: Development of a medium-to-high throughput organoid-bacteria co-culture platform for the assessment of host pathogen interaction
Authors: Eider Valle-Encinas, Roshni Nair, Katerina Pisa, Mayke Doorn, Farzin Pourfarzad, Lani San Mateo, Nicole Desch, Prashanth Gokare, David Pocalyko, Sylvia F. Boj, Carla Verissimo
Journal: Cancer Research (2023)

Abstract Pathogens such as colibactin-producing bacteria strains of the Enterobacteriaceae family are highly prevalent in the gut microbiota of colorectal cancer (CRC) patients. HUB patient derived Organoids, (HUB-OrganoidsTM or PDOs) are self-organized epithelial cell structures with near-physiological features, extensively used to model aspects of cancer initiation and progression. Studies conducted by Pleguezuelos-Manzanos et al. (2020) showed that repetitive cycles of colibactin-producing bacteria into the organoid lumen via microinjection, led to two co-occurring mutational signatures appearance, a single-base substitution signature (SBS-pks) and an indel signature (ID-pks), identified in a subset of CRC patients (~2% and 7%, respectively). These results highlight the relevance of organoids for modelling host-pathogen interactions and the application of these systems as in vitro platforms for investigating long-standing cause-correlation relationship between the presence of genotoxic pathogens and CRC development. The limited scalability of sophisticated co-culture strategies with pathogens such as microinjection has represented a bottleneck in the use of organoids as throughput screening tools in the development of preventive therapies. Thus, there is an unmet need to develop alternative co-culture systems compatible with the process of compound screening. An organoid-bacteria co-culture system compatible with medium-to-high throughput screening readouts has been developed. This co-culture system is currently tailored for the modeling of colibactin genotoxic effects in the gut epithelium, but theoretically could be extended as a discovery platform to identify targetable, novel and complex interactions between host and pathogen. Key words: colibactin, organoids, CRC, screening Citation Format: Eider Valle-Encinas, Roshni Nair, Katerina Pisa, Mayke Doorn, Farzin Pourfarzad, Lani San Mateo, Nicole Desch, Prashanth Gokare, David Pocalyko, Sylvia F. Boj, Carla Verissimo. Development of a medium-to-high throughput organoid-bacteria co-culture platform for the assessment of host pathogen interaction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5917.